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Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage.

ABSTRACT: Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in order to facilitate its rapid recruitment to sites of DNA damage and could explain why an absence of lamin A/C accelerates aging.

SUBMITTER: Gibbs-Seymour I

PROVIDER: S-EPMC4364828 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage.

Gibbs-Seymour Ian I Markiewicz Ewa E Bekker-Jensen Simon S Mailand Niels N Hutchison Christopher J CJ

Aging cell 20150123 2

Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in orde ...[more]

PMID: 25645366

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